"We find that this drug inhibited melanoma from becoming more aggressive in human cells and in experimental models. We also found a specific pathway that this drug acts through to be anti-cancer: inhibiting proteins that drive genes that promote cancer cell growth and metastasis," explained corresponding author Deborah Lang, PhD, associate professor of dermatology at BUSM.

Melanoma is an aggressive cancer type, with a high propensity for invasion and metastasis early in the disease process. There are several factors that actively drive melanoma progression including MET, a tyrosine kinase receptor overexpressed in melanoma and implicated in tumor growth, invasion and drug resistance.

Researchers utilized human cells in culture to determine if there were impactful changes on pro-cancer behavior in these cells with or without the drug YK-4-279 and found a significant reduction in growth and movement of the cancer cells when using it. In addition, experimental models treated with the drug had significantly delayed or no progression to aggressive disease.

According to the researchers these findings create the opportunity for YK-4-279 to be an option for melanoma treatments, either singularly or in combination with other available therapeutics. "We find that this molecule disrupts the interaction of two factors known to regulate melanocytes and promote melanoma through gene regulation. This work may impact other systems where these factors play a role, such as in the nervous system and in pigmentary disorders."

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Materials provided by Boston University School of Medicine. Note: Content may be edited for style and length.

Journal Reference:

1. Lee Huang, Yougang Zhai, Jennifer La, Jason W Lui, Stephen P.G. Moore, Elizabeth C Little, Sixia Xiao, Adil J Haresi, Candice E Brem, Jag Bhawan, Deborah Lang. Targeting pan-ETS factors inhibits melanoma progression. Cancer Research, 2021; canres.1668.2019 DOI: 10.1158/0008-5472.CAN-19-1668